HIV/AIDS
Conditions
Interventions
Placebo
Sponsors
South African Medical ResearchCouncil
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Eligibility criteria Maternal inclusion criteria 1) Documented HIV-1infection antenatally or at delivery and receiving ART as per national guidelines 2) Greater than or equal to18 years of age 3) Breastfeeding at the time of enrolment or willing to initiate breastfeeding in the immediate post-partum period INFANT ELIGIBILITY CRITERIA 1) Gestational age greater or equal to36 weeks, assessed using dual methods of early sonar AND birth Ballard Score (done up to 42 hours after birth) 2) Birth weight greater than or equal to 2.0 kg and lower than or equal to 4.5kg 3) Written consent of one or both parents (according to South African regulation)
Exclusion criteria
Exclusion criteria: Mother exclusion criteria 1) Prior participation in anyHIV-1 vaccine trial 2) Receipt of another active or passive HIVimmunotherapy or investigational product concurrently 3) Documented or suspected serious medical illness with fatal compromise or immediate life-threatening condition (other than HIV-infection as judged by the examining clinician) 4) Unable or unwilling to provide a signed informed consent to participate to the study for herself and her infant 5) Known active tuberculosis or other opportunistic infection 6.Plan to relocate in 1 year or do not have a local address 7)Does not have her own cell phone 8)Not able to provide three alternate contact phone numbers 9) Multiple pregnancies, i.e. twins, triplets, quadruplets, etc. 10) Unwilling or unable to comply with the schedule of activity Infant exclusion criteria 1) Receipt of or anticipated need for blood product, immunoglobulin, or immunosuppressive therapy. This includes infants who require hepatitis immunoglobulins (HBIG) but not infants who receive hepatitis Bvaccine in the new-born period 2)Documented or suspected serious medical or immediate life-threatening condition 3) Infant in ICU or high care requiring supplemental oxygen at time of bNAb dose 4) Known allergy to study drug or components 5) Baseline laboratory results on all neonates -Hemoglobin level less than 12.0 g/dL- Platelet count less than 100,000cells/mm3 - Absolute neutrophil count: for infants less than 24 hours old, less than 4,000 cells/mm3; for infants greater than 24 hours old, less than1,250 cells/mm3 - Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase ALT) greater than or equal to 1.25 times the upper limit of age-adjusted normal Infant: 0 Month-23Month 36 Week(s) 12 Month(s) Both
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| SAE among group 1: this single-stage phase 2 trial relies on the demonstration that the proportion of infants (P) using VRC07-523LS will meet an expected low level or be free of SAE (p(1), the background level in the absence of bNAbs) which is higher than a second proportion level p(0), indicating that the safety level is unacceptable. This p(0) is the level under which we will reject the use of VRC07-LSfor safety issues. The trial tests the null hypothesisH0: P =p(0) against the alternative hypothesis H1: P>p(1). It sets an appropriate cut-off between p(0) and p(1), providing a critical number of participants without SAE which will be used to move on to a Phase 3 trial or not. | — |
Secondary
| Measure | Time frame |
|---|---|
| Among HIV-infected children, we will assess the virological success at 6 months post-delivery. We will adopt the same approach as primary endpoints for the evaluation of virological success in group 3,based on the single-stage A’Hern design. In this case, p(0) will be the minimum rate of children with virological success we can accept, and p(1) is the expected rate of children with virological success. Although some local data provide some indications on the potential value of p(0) (K. Technau Lancet HIVpaper), we will use group 4 to assess p(0) in the trial context, using a randomisation for group allocation to get very comparable groups 3 and 4. Although we want to make sure that the virological success rate will not be hampered by bNAbs, we expect an improvement in the response to treatment due to the early neutralization of HIV virions. This bNAbs activities expected to reduce the HIV RNA load, which is associated with a greater virological response at 6months post-ART initiation (ref). The trial tests the null hypothesis H0: P p(1) | — |
Countries
South Africa
Contacts
Public ContactKerusha Chunderduri
Quality and Regulatory Coordinator
Outcome results
None listed